Similar to other encapsulated pathogens, serum anti-capsular antibodies confer immunity to invasive meningococcal diseases. Group A meningococcal disease has a different epidemiological pattern than the other two major pathogenic meningococcal Groups B and C. In central Africa, Group A diseases are endemic with a high frequency. In other parts of the world Group A causes epidemics, lasting 1-2 years. In both cases asymptomatic carriage of Group A organisms is low. In the U.S., Group A meningococcal diseae has been virtually non-detected in the past 25 years, yet most children and adults have protective levels of Group A antibodies. Investigations to elucidate the basis of the natural immunity to meningococcus Group A showed 11 E. coli strains of 645 stool isolates were cross-reactive with meningococcus Group A. These strains were serotyped, their polysaccharides purified and their structures and immunological cross-reactivities studied. The structure and the immunological properties of the previously identified cross-reactant, B. pumilis (SH17) were compared as well. Ten of the 11 strains were found to be K93: 0107: H27, one was K51: 07: H18. None produce enterotoxin or were invasive. Antisera were raised to the two E. coli types and to SH17. Double immunodiffusion and quantitative precipitin analysis showed partial identity between meningococcus Group A polysaccharide and each of the cross-reactants and non-identity among themselves. Preliminary structural analysis showed the K93 polysacharide to be composed of 3-D gal f-1-4 BetaD-glucuronic acid. The K51 is a polymer of AlphaD-glucosamine phosphate. Antibodies elicited by these E. coli strains precipitated with and were bactericidal against meningococcus Group A.